Attilio GUARINIU.O.C. EMATOLOGIA

Istituto di Ricovero e Cura a Carattere Scientifico

"ISTITUTO TUMORI GIOVANNI PAOLO II“

BARI

I linfomi di HodglinCriticità nel percorso diagnostico

Hodgkin Lymphoma

ØHistologic hallmark of the disease is the presence of the characteristic Hodgkin Reed-Sternberg (HRS) cells in classical HL and so-called lymphocyte-predominant (LP) cells in nodular lymphocyte-predominant HL

ØHL is unique among all cancers because malignant cells are greatly out numbered by reactive cells in the tumor microenvironment and make up only approximately 1% of the tumor

Ø Most patients can be cured with modern treatment strategies, although approximately 20% still have low therapeutic choices, especially after high-dose chemotherapy and haematopoietic stem cell support

represents the most common malignant lymphoma in young people

Classical HL: Morphology

Nodular sclerosisLymphocyte rich

Mixed cellularity Lymphocyte

depleted

Classical HL: Phenotype

CD30

CD15

Phenotypic Profile of cHL

CD3

PAX5

CD20

IRF4

Nodular Lymphocyte Predominance Hodgkin Lymphoma

Morphologic gray zones in HL and NHLs

PERCORSO DIAGNOSTICO

NOAGOASPIRATIFNAB

Non accettare diagnosi se non su biopsie escissionali

LA DIAGNOSI DI HODGKIN DEVE ESSERE

SEMPREUNA DIAGNOSI “PATOLOGICAMENTE” DOCUMENTATA

a livello di morfologia ed immunoistochimica (biologia molecolare)

DECISIONE TERAPEUTICA

Istotipo

VALUTAZIONE CLINICA E PROGNOSTICA

“TAILORED THERAPY”

goal

Diagnostic Workup

• History • Complete physical examination• Confirmatory workup

Ø Excisional biopsy of the lymph node

Staging Workup

Ø Chest x ray(pa,lat)Ø CT scan thorax,abdomen and pelvisØ FDG PET scan

Ø Complete blood countØ Liver functionØ Renal functionØ Serum albuminØ ESRØ Lactate Dehydrogenase

Ø Bone marrow biopsy (?)

PET Scan has become an integral component of initial staging.

Information provided by PET has been recently incorporated in the lymphoma guidelines for response evaluation after completion of treatment.

Useful for follow up study to evaluate residual masses , dx of early recurrence and predicting outcome.

Ann Harbor Stage

Prognostic Factors

Prognostic factor for Early stage Hodgkins disease

Prognostic factors cont…

Advanced stage hodgkins lymphoma International Prognostic Score

Andrea Gallamini, Martin Hutchings, Luigi Rigacci, Lena Specht, Francesco Merli, Mads Hansen, et al.

PET-2 overshadows the prognostic value of IPS and emerges as the single most important tool for planning of risk-adapted treatment in advanced HL

Management

Eichenauer DA et Al, Annals of Oncology 25 (Supplement 3): 70–75, 2014

Anni 70

• MOPP• ABVD

Anni 80

• MOPP/ ABVD

• Stan• ford V

Anni 90

BEACOPP

Anni 2000

moAb

Biology of Brentuximab Vedotin

Vaklavas C & Forero-Torres. Ther Adv Hematol 2012;3:209-225

Younes A et al. J Clin Oncol. 2012;30: 2183-2189 P

Phase II Pivotal Study of Brentuximab VedotinMaximum Reduction in Target Lesions

94% patients achieved tumour reduction

Modern RT

Weber et al, IJROBP 2009

INRT planning

Koeck et al, IJROBP 2011

20 CT datasets of pts with early unfavorable mediastinal HL

IF-PTV and IN-PTV according GHSG guidelines

Plans:- 3D-CRT (AP-PA)- IMRT (9 equally spaced beams)

Prescription dose: 30 Gy/15 fx

0%10%20%30%40%50%60%70%80%90%

100%

5-y EFS 87%

5-y EFS 89%

5-y EFS 90%

5y- EFS 88%

Evolution of Radiotherapy within the

BEACOPP GHSG Trials

outcomes in HL

Cancer 2014;120:2122-9

HL: Cumulative Survival (Sweden)

Intergroup Trial E2498

5-year FFS values of 82% to 89% were reported with dose- and time-intensified third-generation schedules (BEACOPP), but these improvements have so far not been extended to elderly patients.

Advanced age at presentation is an independent negative risk factor.

…. survival rates for elderly Hodgkin lymphoma (>=60 years), are disproportionately inferior compared with younger patients

Two hypotheses were created to explain these findings:

1) age associated factors: - increased comorbidity,

- reduced tolerability of conventional therapy,

- more severe toxicity

- treatment-related deaths,

- poorer outcome after relapse

2) biologic differences such as • more aggressive histology, • different anatomic distribution of involved sites, and • shorter history of disease (greater frequency of mixed cell disease and

Epstein-Barr virus–related disease)

Hodgkin's Lymphoma in the Elderly: Different Disease in Patients Over 60!By Volker Diehl and Andreas Engert -German Hodgkin Study Group  

Linfoma di Hodgkin: 42.000 pazienti

34.000 vivi dopo 5 anni“hodgkin survivors”

• Pazienti giovani• Follow up lunghi• Remissioni dopo radio-chemio terapie intensive

– MOPP / extended field RT / BEACOPP

• Follow up di trapianto autologo e allogenico• Immunosoppressione

Registro AIRTUM 2013

Il rischio di morte per linfoma dopo circa 10 anni dalla terapia, raggiunge un plateau

Mentre il rischio di mortalità dovuta alle complicanze tardive legate al trattamento, continua ad aumentare dopo 10-20 anni e non vi è un plateau

Ng AK et al. N Engl J Med 2010;363:664-675.

le principali cause di mortalità :

– Seconde neoplasie– Eventi cardiovascolari

le principali cause di morbidità :– Disturbi respiratori– Disfunzioni ormonali– Infertilità – Fatigue

►18.5 incremento di rischio di sviluppare seconde neoplasie comparate con la popolazione generale

HL: Complicanze tardive - Neoplastiche

v GIv Polmonev Mammellav Cutev Testa collov Vescicav Tiroide v SNC

Dutch HL cohort 1965-95

cosa si aspettano i clinici dal Registro Tumori

• Integrare i dati prodotti dai registri di “patologia”

• Consentire di seguire nel tempo i pazienti con maggiore continuità

• Consentire stime aggiornate sulla prognosi dei pazienti

• Possibilità di utilizzare i dati per gli studi retrospettivi

Grazie per l’attenzione